Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) and trichloroethylene (TCE) pose significant health risks and enduring remediation challenges. For example, extensive PCB contamination at the Paducah Gaseous Diffusion Plant, the largest Superfund site in Kentucky, is of major concern for its health consequences. The University of Kentucky Superfund Research Center (UK-SRC) provides a focused transdisciplinary research, training and translation environment to address human health challenges associated with such exposures. Preliminary findings suggest that nutrition-based concepts and exercise can markedly influence the mechanisms of toxicity of chlorinated organics. Indeed, healthful nutrition/nutritional components may provide a platform to develop primary prevention strategies for diseases associated with environmental toxic insults, while also providing the basis for new risk assessment paradigms. Further, novel iron-based, nano-structured capture/sensing and remediation systems based on biomimetic binding domains and functionalized/responsive membrane platforms offer potential for sustainable advances in technical capability for site remediation. The UK-SRC proposes to reduce risk by: 1) developing lifestyle-related modulators of environmental disease and elucidating relevant protective mechanisms, and 2) developing technologically effective and economically efficient methods for capture/sensing and remediation of PCBs. Three biomedical and two environmental science projects, a Research Support Core, and Administrative, Research Translation, Community Engagement and Training Cores collectively advance understanding of toxicant-induced mechanisms of disease, introduce sustainable approaches for remediation and enhance stakeholder and community capacity to act. Biomedical projects focus on models of inflammation and associated changes in redox status and inflammatory cytokines in vascular (Project 1), fetal (Project 2) and adipose (Project 3) tissues with relevance to atherosclerosis, insulin resistance/diabetes and obesity. Environmental science projects employ nanomaterials to create selective PCB-binding domains with high affinity and selectivity for PCBs (Project 4) and a functionalized polymer immobilized membrane platform to support PCB dechlorination (Project 5). All Projects focus on common PCB toxicants. Biomedical scientists, with the Research Support Core, also evaluate byproducts of environmental science projects for unintended effects. Use of PCBs as a model contaminant will advance understanding of inflammatory diseases associated with exposure to persistent chlorinated organic pollutants. Research results will lead to evidence-based multidirectional information/education, technology transfer, training, policy and translational activities via UK-SRC cores. Expected outcomes include positive lifestyle interventions across the lifespan for populations at risk and advanced technical capacity to reduce public health risks.